It is known that
tumor antigens could induce obvious anti-
tumor immune responses for efficient
cancer immunotherapy when combined with checkpoint blockade. However, the amount of
tumor antigens is often limited due to the suppressive tumor microenvironment (TME). Here, a new type of nanomaterial was developed to improve
tumor treatment by the combined action of starving
therapy/photodynamic therapy (
PDT)/
photothermal therapy (PTT) and checkpoint-blockade
immunotherapy. In detail, the
immunoadjuvant nanoagents (γ-
PGA@GOx@Mn,Cu-CDs) were fabricated by integrating the gamma-glutamyl
transferase (GGT)
enzyme-induced cellular uptake
polymer-poly (γ-
glutamic acid) (γ-
PGA), a
glucose-metabolic reaction agent -
glucose oxidase (GOx), Mn,Cu-doped
carbon dots (CDs) as
photosensitizer and self-supplied
oxygenator nanodots. γ-
PGA@GOx@Mn,Cu-CDs nanoparticles (NPs) showed long retention time at the
tumor acidic microenvironment and could further target
cancer cells. The NPs also displayed both photothermal and photodynamic effects under
laser irradiation at 730 nm. Interestingly, the endogenous generation of
hydrogen peroxide (H2O2) caused by the nanoreactors could significantly relieve tumor hypoxia and further enhance in vivo
PDT. By synergistically combining the NPs-based starving-like
therapy/
PDT/PTT and check-point-blockade
therapy, the treatment efficiency was significantly improved. More importantly, the systematic antitumor immune response would eliminate non-irradiated
tumors as well, which is promising for
metastasis inhibition.